From Resistance to Renewal: Design Strategies and Structure–Activity Relationships of Novel EGFR Inhibitors in Breast Cancer: Mini Review

Vollständiger Abstract

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ABSTRACT Breast cancer continues to be one of the top causes of cancer death globally, with triple‐negative breast cancer (TNBC) being the most aggressive variety as it has a much poorer prognosis, strong propensity for metastases, and fewer effective targeted therapies available. The increased expression of the epidermal growth factor receptor (EGFR) is essential for cancer cell growth, survival, migration, and drug resistance making EGFR a good target for therapy. However, the effectiveness of EGFR inhibitors has been limited because of heterogeneity of tumors, low occurrence of activating EGFR mutations, and activity of compensatory pathways. This mini‐review aims to summarize new findings on the design of small molecules that inhibit EGFR including pyrimidine‐5‐carbonitrile, thiazolyl‐pyrazolines, quinoxaline, quinazoline–sulfonamide hybrids, xanthine–chalcone conjugates, aminoquinolines, and pyridazine analogues. Their pharmacological properties, interactions with EGFR in silico and important structural characteristics responsible for their therapeutic action will also be discussed. Possible approaches for overcoming acquired resistance, including covalent and allosteric inhibitors, dual‐acting compounds, and combination therapies will be presented here.